Tumor Inhibiting [1,2‐Bis(difluorophenyl)ethylenediamine]‐dichloroplatinum(II) Complexes, I: Synthesis

Müller, Richard; Schickaneder, Edith; Jennerwein, Margaretha; Reile, Herta; Spruß, Thilo; Engel, Juergen; Schönenberger, Helmut

doi:10.1002/ardp.19913240211

Cited by 6 publications

(1 citation statement)

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“…Meso-1-PtSO 4 [35], meso-2-PtSO 4 [36], meso-3-PtSO 4 [37,38] and their PtCl 2 derivatives, meso-4-PtCl 2 [39], meso-5-PtCl 2 [40] were synthesized as described previously.…”

Section: Drugs For Comparative Kinetics and Pharmacological Studiesmentioning

confidence: 99%

[1, 2‐Bis(2, 6‐difluoro‐3‐hydroxyphenyl)ethylene‐diamine]platinum(II) Complexes, Compounds for the Endocrine Therapy of Breast Cancer ‐ Mode of Action II: Contribution of Drug Inactivation, Cellular Drug Uptake and Sterical Factors in the Drug‐Target Interaction to the Antitumor Activity

Schertl

Hartmann

Batzl‐Hartmann

et al. 2004

Archiv der Pharmazie

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The marked activity of [meso-1, 2-bis(2, 6-difluoro-3-hydroxyphenyl)ethylenediamine]platinum(II) (meso-3-PtLL', L, L' = Cl(2) or L = OH(2), L' = OSO(3)) on the hormone-sensitive MXT-M-3, 2 breast cancer implanted in mice is most probably due to a mechanism based on the reduction of the endogenous estrogen level. Cytotoxic effects which are poorly pronounced in experiments on several breast cancer cell lines (e.g. MCF-7), do not significantly contribute to the anti-breast cancer activity of this compound. In contrast to this, the standard cisplatin and the structurally related comparison compound [meso-1, 2-bis(4-fluorophenyl)ethylenediamine]platinum(II) (meso-4-PtLL', L, L' = Cl(2) or L = OH(2), L' = OSO(3)) are strongly active in vivo as well as in vitro. Both effects entail programmed cell death, which is responsible for the inhibition of the tumor growth. The minor cytotoxicity of meso-3-PtLL' in breast cancer cell cultures is caused neither by an inappropriate rate of reaction with bionucleophiles (e.g. by a too fast inactivation by plasma proteins) nor solely by the observed poor absorption by the tumor cells resulting in an insufficient drug concentration at the DNA. Additionally, an impeded reaction with biologically important, guanine-rich sequences of DNA (owing to the 2, 6-standing F atoms which hinder the drug-target inter action) must be assumed as cause of its marginal cytotoxicity.

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“…Meso-1-PtSO 4 [35], meso-2-PtSO 4 [36], meso-3-PtSO 4 [37,38] and their PtCl 2 derivatives, meso-4-PtCl 2 [39], meso-5-PtCl 2 [40] were synthesized as described previously.…”

Section: Drugs For Comparative Kinetics and Pharmacological Studiesmentioning

confidence: 99%

[1, 2‐Bis(2, 6‐difluoro‐3‐hydroxyphenyl)ethylene‐diamine]platinum(II) Complexes, Compounds for the Endocrine Therapy of Breast Cancer ‐ Mode of Action II: Contribution of Drug Inactivation, Cellular Drug Uptake and Sterical Factors in the Drug‐Target Interaction to the Antitumor Activity

Schertl

Hartmann

Batzl‐Hartmann

et al. 2004

Archiv der Pharmazie

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1,3‐Diphenylpropane‐1,3‐diamines, V: ¹H‐NMR‐ and IR‐Spectroscopic Data of 1,3‐Diphenylpropane‐1,3‐diamines and their Pt(II) Complexes: Stereochemical Assignments and Binding Mode of the Non‐amine Ligands

Kammermeier

Wiegrebe

1994

Archiv der Pharmazie

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The 'H-NMR spectra of some 1,3-diacetamino-l.3diphenylpropanes and of the dichloro-Pt(II) complexes of the corresponding diamines are compared with their simulated spectra leading to the stereochemical assignments meso / ruc and eryrhrolthreo, respectively.-IR-spectra data of our "diaqua/sulfato complexes" indicate coordinated as well as free (counterionic) sulfate.'H-NMR-und IR-spektroskopische Untersuchungen an 1,3-Diphenylpropan-1,3-diaminen und lhren Pt(I1)-Komplexen: Stereochemische Zuordnung und Bindung der nicht-aminischen Liganden Die 'H-NMR-Spektren einiger 1,3-Diphenylpropan-l,3-diamine und ihrer Dichlor-Pt(l1)-Komplexe wurden mit den berechneten Spektren verglichen und fiihrten so zu den stereochemischen Zuordnungen meso / ruc bzw. erythro/threo.-Die IR-spektroskopischen Daten unserer "diaqua/sulfato Komplexe" weisen auf koordiniertes und freies (gegenionisches) Sulfat in diesen Verbindungen hin.In part 111') of this series we have reported on the syntheses of the title ligands, while part IV2) deals with the preparation of their Pt(1l) complexes with C1', I, SOj2., and water as additional 1igands.-The 'H-NMR spectra of the ligands and their F't complexes have been compiled in the Experimental Parts of these publications, and the ligands were assigned meso / ruc, and eryrhrolthreo, respectively, without giving an explanation for these indications.Here we describe the arguments of these assignments based on 'H-NMR measurements. Because we are dealing with complicated spin systems with various nuclei, the assignment of the protons by conventional methods is difficult in most cases. Therefore, we have simulated the spectra with the help of a Comparex 8/85 computer (system VM/CMS 5.0) using the program LAME (LAOCOON with Magnetic Equivalence). This is a variation of LAOCOON3) modified by Haigh, Swansea College, Knorr, Munchen, and Poppinger and Vollmerhaus-Koschnik, Regensburg (unpublished). LAME considers nuclei of spin 1/2 only and maximally accepts seven groups of magnetically equivalent spins. If one or several of these groups contain more than one spin, there are additional limitations.At first LAME calculares a theoretic spectrum with line frequences and line itensities in a non-iterative run, using a set of estimated chemical shifts and J-values. In most cases this spectrum does not yet fit the observed one. So, in an iterative run the frequence of a line of the experimental spectrum is attributed to the number of each calculated line. This step is decisive for a good result and, therefore, the lines are attributed according to Hoffmunn et u/!). The subsequent calculation is based on the *) Dedicated to Prof. Dr. H. J . Roth, Tiibingen, on the occasion of his 65th birthday.assumption, that the set of parameters is the best one "which make the sum of the squared residuals of the observables (in this case, transition frequencies) a minim~m"~). k: number of observed linesVeXp -fcalc): difference of frequencies between observed and calculated transition LAME then looks for alterations of those parameter...

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ChemInform Abstract: Tumor Inhibiting (1,2‐Bis(difluorophenyl)ethylenediamine) dichloroplatinum(II) Complexes. Part 1. Synthesis.

Mueller¹,

Schickaneder²,

Jennerwein³

et al. 1991

ChemInform

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Tumor Inhibiting [1,2‐Bis(difluorophenyl)ethylenediamine]‐dichloroplatinum(II) Complexes, I: Synthesis

Cited by 6 publications

References 4 publications

1,3‐Diphenylpropane‐1,3‐diamines, V: ¹H‐NMR‐ and IR‐Spectroscopic Data of 1,3‐Diphenylpropane‐1,3‐diamines and their Pt(II) Complexes: Stereochemical Assignments and Binding Mode of the Non‐amine Ligands

ChemInform Abstract: Tumor Inhibiting (1,2‐Bis(difluorophenyl)ethylenediamine) dichloroplatinum(II) Complexes. Part 1. Synthesis.

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Tumor Inhibiting [1,2‐Bis(difluorophenyl)ethylenediamine]‐dichloroplatinum(II) Complexes, I: Synthesis

Cited by 6 publications

References 4 publications

1,3‐Diphenylpropane‐1,3‐diamines, V: 1H‐NMR‐ and IR‐Spectroscopic Data of 1,3‐Diphenylpropane‐1,3‐diamines and their Pt(II) Complexes: Stereochemical Assignments and Binding Mode of the Non‐amine Ligands

ChemInform Abstract: Tumor Inhibiting (1,2‐Bis(difluorophenyl)ethylenediamine) dichloroplatinum(II) Complexes. Part 1. Synthesis.

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1,3‐Diphenylpropane‐1,3‐diamines, V: ¹H‐NMR‐ and IR‐Spectroscopic Data of 1,3‐Diphenylpropane‐1,3‐diamines and their Pt(II) Complexes: Stereochemical Assignments and Binding Mode of the Non‐amine Ligands